(a) Field of Invention
The present invention relates generally to a novel process for making certain known biologically active heterocyclic benzamide compounds. More particularly, the present invention is concerned with a novel process for producing imidazo[2,1-a]isoindoles of the general formula I: ##STR2## wherein X represents hydrogen, halogen in particular fluorine, chlorine and bromine, or lower alkoxy.
(b) Description of Prior Art
Imidazo[2,1-a]isoindoles of the general formula I and processes for their production are generally described, for example, in U. K. specifications Nos. 1,225,411 1,225,412 and 1,225,413.
In these specifications such imidazo [2,1-a] isoindoles are described as being biologically active and are indicated as having utility as psychic energizers and anorectics. Probably the best known of such compounds at the present time is 5-(p-chlorophenyl)-2,3-dihydro-5-hydroxy- 5H-imidazo[2,1-a]isoindole commonly referred to as mazindol.
The prior art discloses several processes for obtaining the compounds of formula I but these processes all leave something to be desired. For example, the processes disclosed in the above specification usually involve the reduction of an intermediate carbonyl compound followed by a very delicate oxidation. The process steps, and especially the latter, are very time consuming. Although the specifications teach that the oxidation step may be effected within a relatively short time by bubbling air or oxygen it should be noticed that the specifications emphasize, and all but one of the detailed specific examples illustrate, a very mild oxidation wherein the reaction mixture is merely contacted with air over a period of many, usually six, days. Since the simple procedure of bubbling a gas, especially air, through a reaction mixture generally presents few problems, the emphasis on the use of the very long oxidation step indicates that this procedure is highly preferred. The above processes also utilize lithium aluminum hydride as the agent to reduce the intermediate carbonyl function. This reagent is very expensive and, moreover, presents a significant fire hazard which, on a small scale, may be acceptable. However, the use of that reagent on a large, i.e. commercial, scale is very hazardous and involves significant inconvenience and expense. It may also be noted that the above specifications refer to process yields only in general terms and as being "appreciable". There is no specific yield given in any of the said three specifications and, although a much later reference (J. Med. Chem. 18, 177, (1975)) indicates that a yield of 65% is possible for the oxidation step, the present Applicant did not obtain a yield of even half that amount using the same process.